The proposed study will have three primary objectives: A. Extension of previous studies of the nature of the immunoglobulin produced by the lymphocytic infiltrate in the rheumatoid synovium. The large amount of IgG synthesized in vitro by fragments of rheumatoid synovival tissue will be further studied for its homogeneity with respect to light chain type, subclass and antigen binding specificity, particularly against viral and bacterial antigens. B. Study of the role of rheumatoid factor and complement on modification of the chronicity of the synovitis in a rabbit model of rheumatoid arthritis. The solubility of immune complexes has recently been shown to be drastically altered by continued exposure to excess C3 which causes their dissolution. Since rheumatoid factor (RF) may block complement fixation, its role in the enhancement of local trapping of antigen-antibody complexes in joint tissues will be evaluated in a rabbit model in which the animals have been made tolerent to human IgM at birth. C. Further evaluation of common human viruses as possible antigen(s) responsible for rheumatoid synovitis will be made. Paired serum-synovial fluid samples from patients with active RA and joint effusion will be passed over agarose columns containing immobilized IgG to remove RF. Each pair will then be compared for their antibody titers (relative to their IgG content) against viral antigens which may cause rheumatoid synovitis. Work recently completed in this laboratory has shown an unexpected elevation of titers of CF antibody against Influenza B in the sera of rheumatoid arthritis patients when compared with the sera of matched controls after the RF had been moved. The rheumatoid sera were entirely negative against this virus prior to RF adsorption.